B(C6F5)3/CPA-Catalyzed Aza-Diels-Alder Reaction of 3,3-Difluoro-2-Aryl-3H-indoles and Unactivated Dienes.

Here we report B(C6F5)3/CPA-catalyzed enantioselective aza-Diels-Alder reaction of 3,3-difluoro-2-Aryl-3H-indoles with unactivated dienes to access chiral 10,10-difluoro-tetrahydropyrido[1,2-a]indoles. This protocol allows the formation of pyrazole-based C2-quaternary indolin-3-ones with high enantioselectivities and regioselectivities. Moreover, gram-scale synthesis of the 10,10-difluoro-tetrahydropyrido[1,2-a]indole skeleton was successfully achieved without any reduction in both yield and enantioselectivity.

Highly Enantioselective Synthesis of 3a-Fluorofuro[3,2-b]indolines via Organocatalytic Aza-Friedel-Crafts Reaction/Selective C-F Bond Activation.

Fluoroalkylated compounds are of high interest in drug discovery and have inspired the evolution of diverse C-F bond activation methodologies. However, the selective activation of polyfluorinated compounds remains challenging. Herein, we describe an unprecedented strategy for synthesizing enantioenriched fluorofuro[3,2-b]indolines through the organocatalytic aza-Friedel-Crafts reaction coupled with selective C-F bond activation. These reactions feature excellent enantioselectivities (≤96% ee) and yields (≤96%) as well as good functional group compatibility. Mechanistic investigations by means of 19F nuclear magnetic resonance experiments provided sufficient support for silica gel as the key medium in this transformation.

Anti-freezing dual-network hydrogels with high-strength, self-adhesive and strain-sensitive for flexible sensors.

Hydrogels as flexible sensor have attracted significant attention due to its conductivity, stretchability and flexibility. However, it is still a great challenge to prepare hydrogels that simultaneously possess high strength, anti-fatigue, self-adhesion, and anti-freezing. Herein, a multifunctional dual-network hydrogel was prepared by in situ polymerization of acrylic monomer in chitosan chains, and coordinated with aluminum chloride and glycerol. Based on chain entanglement, hydrogen bonding and coordination interactions, this dual-network hydrogel exhibited excellent mechanical properties, good fatigue resistance, and excellent adhesion performance. It can be used as a strain sensor for its stable conductivity and high sensitivity, which could monitor both large human motions and subtle motions. Due to the presence of glycerol, the hydrogel showed outstanding freezing resistance and still kept flexible and conductive even at low temperatures (-20 °C). This hydrogel can be applied as a flexible wearable sensor for monitoring human motion in extreme low-temperature condition.

SOAT1 is a new prognostic factor of colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant gastrointestinal cancers. Metastasis is the major leading cause of death in patients with CRC, and many patients treated with radical surgery were diagnosed with metastasis during follow-up. However, the underlying molecular mechanisms regulating CRC metastasis are still elusive. Sterol o-acyltransferase 1 (SOAT1) is a critical participant in maintaining intracellular cholesterol balance. Here, by analyzing the clinical specimens and in vitro cell line experiments, we evaluated the clinical relevance and role of SOAT1 in regulating CRC metastasis. The results revealed that SOAT1 was overexpressed in colon cancer tissues compared to peritumor tissues at mRNA and protein levels. High intratumor SOAT1 expression correlates to lymph node metastasis and indicates poor patient disease-free survival and overall survival. The silencing of SOAT1 strongly inhibited the migration and invasion ability of CRC tumor cells. These results demonstrated that SOAT1 was upregulated in colon cancer. Upregulation of SOAT1 expression may promote CRC progression by enhancing the migration and invasion ability of CRC. Our results indicate that targeting SOAT1 activity may be applied as a promising therapeutic strategy for preventing the metastasis of CRC after radical surgical treatment.

Prediction of Peking duck intramuscle fat content by near-infrared spectroscopy.

Peking duck is the most representative of the meat-type duck breed, and it is also one of the most popular meats in Asia. Few studies were reported on the fast assessment of duck meat quality. This study aimed to develop a fast measuring of duck fat content by using the near-infrared spectroscopy (NIRS) method. We measured 273 duck breast muscle intramuscle fat (IMF) content and spectra. Partial least-squares regression (PLSR) was used to model the fat content prediction by using the spectra in the wavelengths between 950 and 1650 nm. The best predictive abilities were obtained after the first derivative pretreatment, with coefficient of calibration (R2C) of 0.92, with coefficient of prediction (R2P) of 0.90, ratio performance to deviation (RPD) of 2.72, and ratio of error range (RER) of 15.45, for samples of 30 g duck. Results demonstrated that the near-infrared spectroscopy is a useful tool for fat content assessment of Peking duck meat.

Shaoyao-Gancao Decoction alleviated hyperandrogenism in a letrozole-induced rat model of polycystic ovary syndrome by inhibition of NF-κB activation.

Shaoyao-Gancao Decoction (SGD) has been widely used for the treatment of gynopathy. The present study aimed to evaluate the therapeutic effect and potential mechanism of SGD on hyperandrogenism in polycystic ovary syndrome (PCOS) rats. In the present work, SGD was orally administrated to the PCOS rats at the dose of 12.5, 25, and 50 g/kg/d for 14 consecutive days. UPLC-MS/MS was performed to identify the main chemical components of SGD. Body weight, ovarian weight, cystic dilating follicles, and serum levels of steroid hormones were tested to evaluate the therapeutic effect of SGD. In order to further clarify the underlying mechanism, we also measured mRNA and the protein levels of NF-κB, NF-κB p65, P-NF-κB p65, and IκB by RT-qPCR and Western blotting techniques. Our results showed that SGD treatment significantly alleviated hyperandrogenism in PCOS rats as evidenced by reduced serum levels of T and increased E2 and FSH levels. In addition, SGD effectively reduced the phosphorylation of NF-κB p65 and increased the expression of IκB. Results of the present study demonstrated that SGD could ameliorate hyperandrogenism in PCOS rats, and the potential mechanism may relate to the NF-κB pathway.

[Effect of Dracocephalum moldavica total flavones on expression of TGF-ß1/Smad signaling pathway and matrix metalloproteinase of atherosclerosis ApoE-/- mice].

To investigate the effect and mechanism of Dracocephalum moldovica total flavones (TFDM) on the formation of atherosclerosis ApoE-/- mice induced by high fat diet. A total of 40 SPF 8-week-old male ApoE-/- mice were fed with high fat diet and randomly divided into 5 groups. TFDM high, medium, low-dose group were given 21, 42, 84 mg•kg⁻¹â€¢d⁻¹ by gavage; Simvastatin group was fed with simvastatin 3.5 mg•kg⁻¹â€¢d⁻¹; and model group was given the same dose of normal saline. The other eight male C57BL/6J mice of the same genetic background and age were set up as control group and fed with common diet. All of the groups were intragastrically intervened for 12 weeks. The aortic pathologic changes were observed with HE; qRT-PCR was adopted to detect TGF-ß1, Smad2, Smad3, MMP-2 and MMP-9 gene levels in tissues. Compared with model group, HE staining in TFDM group showed obvious relief of aortic atherosclerotic tissue injury; each TFDM group showed inhibition in mRNA expressions of TGF-ß1, Smad2, Smad3, MMP-2 and MMP-9. This suggests that TFDM can inhibit atherosclerosis formation, which may be related to the intervention of TGF-ß1/Smads signal transduction.

[Flavanoids Extracted from Onion Inhibited Activation of Microglia and Release of Proinflammatory Factors around the Hematoma in ICH Model Rats].

OBJECTIVE: To study flavanoids extracted from onion (FEO) on the number of activated microglia and the release of proinflammatory factors in intracerebral hemorrhage (ICH) model rat at different time points, and to explore its possible mechanism for treating ICH. METHODS: Totally 100 Wistar rats were used for preparing ICH model, and ICH model was successfully established in 90 of them. The 90 rats were randomly divided into the sham-operation group (n =10) , the ICH group (n =40) , the FEO group (n =40). Totally 100 [L autoblood was injected from fixed position to rats in the ICH group and the FEO group during modeling. Meanwhile, FEO at 0. 2 mL/10 g was given to rats in the FEO group, twice daily. No drug intervention was given to rats in the ICH group and the sham-operation group. Each group was further sub-divided into 5 sub-groups according to different time points such as 6, 24, 48, 72 h, and 7 days. There were 8 rats in each sub-group of the ICH group and the FEO group, 10 groups in total. There were 2 rats in each subgroup of the sham-operation group, 5 groups in total. Neurological functions at different time points were observed by Garcia JH. The injury degree of brain tissue was observed at dif- ferent time points using HE staining. Activated microglia around hematoma were observed at different time points after ICH by using immunohistochemical staining. Expressions of TNF-α and IL-1 ß at different time points after ICH was detected using ELISA. RESULTS: In the ICH group, degenerated and necrotic zone occurred around hematoma after injecting autoblood, cells were untidily arranged with irregular nucleus, partial nucleus were shrunken with lamellar interstitial edema of the medulla. As time went by, degenerated and necrotic zone was dilated; vacant zone occurred around cells; cells were unevenly distributed with reduced neuron numbers. Meanwhile, infiltration of lymphocytes and neutrophils occurred. In the FEO group after FEO intervention, necrotic cells were lesser, cell arrangement and nucleus morphology were obviously alleviated, and infiltration of inflammatory cells was reduced at corresponding time points. Compared with the sham-operation group, behavioral scores at 5 time points all decreased, the number of activated microglia was added, and expressions of TNF-α and IL-1 ß in hematoma tissue increased in the ICH group (P <0. 01). Compared with the ICH group, behavioral scores at 48 and 72 h, as well as day 7 all increased, the number of activated microglia was reduced, and expressions of TNF-α and IL-1ß in hematoma tissue decreased in the FEO group (P <0. 01). CONCLUSION: FEO using the ethanol reflux method could improve symptoms of ICH model rats possibly by inhibiting activation of microolia and the release of proinflammatory factors around the hematoma.

Optimization modeling of single-chain antibody against hepatoma based on similarity algorithm.

The purposes was to establish optimal modeling of single-chain antibody molecules based on similarity algorithm and seek the connecting peptides that had the minimal effect on the structure and bioactivity of the variable region of heavy chain (VH) and that of light chain (VL) in a single-chain antibody against liver cancer. After the Linker with different lengths (n=0~7) had been added into single chain fragment variable (ScFv), modeling of the overall sequences of VH, VL and ScFv were conducted respectively. Meanwhile, the peptide chain structure of (Gly4Ser)n was adopted for the connecting peptide. Then the spatial spherical shell layer alignment algorithm based on spherical polar coordinates was utilized for comparing the structural similarity of VH and VL before and after adding connecting peptide. Equally, in order to determine the stability of VH and VL, MATLAB was applied for analysis of the fore and aft distances and the diffusion radius. Indirect ELISA method was used to detect single-chain antibody immunological activity of Linker with different lengths. The MTT assay was utilized for the examination of the inhibition rate of single-chain antibody with different lengths of Linker to liver cancer cell. When n=4, the structural similarity between VH together with VL and their original ones was the highest. When n=3, the influence of connecting peptide on the stability of VH and VL was minimum. When n>3, the fore and aft distances changed little due to the increase and fold of the length of peptide chain. The results of ELISA detection showed that when n=4, affinity of single chain antibody to liver cancer cells was much higher. The MTT test also indicated that when n=4, the inhibition rate of the connecting peptide on hepatoma carcinoma cell reached the highest, and that came second when n=3. When n=4, the structural stability and biological functions of anti-hepatoma single-chain antibody were both favorable. This study has provided a basis for the design and construction of single-chain antibody.

Efficacy of Albendazole-Chitosan Microsphere-based Treatment for Alveolar Echinococcosis in Mice.

This study aimed to investigate the pharmacology and anti-parasitic efficacy of albendazole-chitosan microspheres (ABZ-CS-MPs) for established intraperitoneal infections of Echinococcus multilocularis metacestodes in an experimental murine model. Male outbred Kunming mice infected with E. multilocularis Metacestodes were administered with three ABZ formulations, namely, ABZ-CS-MPs, Liposome-Albendazole (L-ABZ), and albendazole tablet (ABZ-T). Each of the ABZ formulations was given orally at three different doses of 37.5, 75, and 150 mg/kg, three times a week for 12 weeks postinfection. After administering the drugs, we monitored the pharmacological performance and anti-parasitic efficacy of ABZ-CS-MPs compared with L-ABZ, and ABZ-T treated mice. ABZ-CS-MPs reduced the weight of tissues containing E. multilocularis metacestodes most effectively compared with the ABZ-T group and untreated controls. Metacestode grown was Highly suppressed during treatment with ABZ-CS-MPs. Significantly higher plasma levels of ABZ metabolites were measured in mice treated with ABZ-CS-MPs or L-ABZ compared with ABZ-T. In particular, enhanced ABZ-sulfoxide concentration profiles were observed in the mice given 150 mg/kg of ABZ-CS-MPs, but not in the mice treated with L-ABZ. Histological examination showed that damages caused disorganization of both the germinal and laminated layers of liver hyatid cysts, demolishing their characteristic structures after treatment with ABZ-CS-MPs or L-ABZ. Over time, ABZ-CS-MPs treatment induced a shift from Th2-dominant to Th1-dominant immune response. CS-MPs As a new carrier exhibited improved absorption and increased bioavailability of ABZ in the treatment of E. multilocularis infections in mice.